An Ebola Drug Trial Ended Early Because It Was So Successful. That Could Change How Doctors Handle Future Outbreaks

A year into an Ebola outbreak in the Democratic Republic of the Congo (DRC), researchers have halted an experimental drug trial there because early results appear so promising. The drugs will be made available to more patients in the DRC, hopefully saving lives as the current outbreak continues. But the decision to end the trial early has implications that go beyond the DRC: it could also change the way infectious disease treatments are studied in years to come.

The trial, which began last November and enrolled 681 patients at four sites in the DRC, was meant to test four experimental Ebola therapies: ZMapp (an antibody cocktail from Mapp Biopharmaceutical), remdesivir (an antiviral from Gilead Sciences), mAb114 (a monoclonal antibody licensed by Ridgeback Biotherapeutics), and REGN-EB3 (another antibody cocktail made by Regeneron Pharmaceuticals). After less than a year, the latter two appeared so successful that an independent board overseeing the trial recommended that it end early, according to an announcement from one of the study’s co-sponsors, the U.S. National Institute of Allergy and Infectious Diseases (NIAID). All future patients in the trial will receive either mAb114 or REGN-EB3, and the drugs will also be available to patients in Ebola treatment centers throughout the DRC.

That’s big news not only because it provides hope that more Ebola patients will survive the often-fatal hemorrhagic fever, which has no previously known cure. Beyond that, the study’s success also provides strong support for the idea of conducting trials in the midst of an outbreak—an idea once seen as controversial.

“Often when you’re in an outbreak, people want to do good and help people, so they’ll give anybody any drug that they have,” says NIAID Director Dr. Anthony Fauci. “You might get a good feeling that you’ve done something for someone, but at the end of the [outbreak] you don’t have any idea what works or what doesn’t work. A randomized controlled trial, he says, provides answers that handing out drugs arbitrarily could not.

After the West African Ebola outbreak that killed more than 11,000 people from 2014-2016, the National Academy of Sciences declared that research in the midst of an outbreak was ethically and scientifically appropriate, and the present trial supports that sentiment, Fauci says. The trial moved quickly because many people were infected with Ebola, making it easy to enroll enough patients, Fauci says. Once researchers enrolled enough patients for a robust study, its results were so convincing that Fauci says it would have been “unethical” to continue giving patients the less-effective drugs.

So far, the DRC Ebola outbreak has infected about 2,700 people and killed roughly 1,850, for a fatality rate of around 67%. Among the roughly 500 study patients analyzed before the trial ended, however, fatality rates were reportedly 34% and 29% after treatment with mAb114 and REGN-EB3, respectively. ZMapp and remdesivir also improved upon the standard mortality rate, but not to the same degree: They lowered death rates to about 49% and 53%, respectively.

Dr. James Lawler, an infectious disease expert at the University of Nebraska Medical Center who has trained Ebola health workers in Uganda, says it’s too soon to say exactly what impact those drugs will have on outbreak response, but agrees that the trial’s promising results—and very existence—are an important step forward.

“It is a major step in outbreak response, to demonstrate that research is an important—really an invaluable—component to improving the care that we deliver,” Lawler says.

Both Lawler and Fauci are careful to note that treating already-sick patients is only one part of an effective public-health response. “You end outbreaks by preventing infection,” Fauci says. That process involves treating existing infections, of course, but it also requires monitoring transmission patterns, identifying people who may have come into contact with sick individuals and using tools like vaccines to prevent illnesses before they start. (Preliminary evidence suggests an experimental vaccine developed by Merck can prevent infection, and it is being used in the DRC and neighboring countries. Another vaccine from Janssen Pharmaceuticals is also being tested in Uganda, and is expected to be deployed in the DRC in the near future.) That’s a difficult undertaking in any context, but continuing violence after a years-long civil war, misinformation and security concerns for health workers in the DRC have made it even more challenging during the current outbreak.

If anything, though, Lawler says those challenging circumstances provide even more support for future mid-outbreak studies.

“Doing clinical trials in ideal settings is difficult. Doing those trials in research-limited settings in the middle of a public-health emergency is even more difficult,” he says. “All of those barriers were overcome in some of the most austere environments that you could potentially devise for an outbreak setting. If we can do it in that setting, I think it demonstrates that we can do it just about anywhere.”